Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activation

Molecular Cancer

Research

Rui Liu¹  Yi-Jie Zhang¹  Gang Li¹  Bin Song¹  Ying-Qi Zhou¹  Cheng-Hao Shao¹  An-An Liu¹  Wei Jing¹  Gang Jin²  Xian-Gui Hu²  Qi Bian³ 

[1] Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China;Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China;

关键词: Pancreatic cancer;    ASSP2;    Proliferation;    Autophagy;    Drug resistance;    Gemcitabine;   

DOI  :  10.1186/s12943-015-0447-5

 received in 2015-04-08, accepted in 2015-09-21,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundApoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear.MethodsWe analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo.ResultsExpression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy.ConclusionsASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.

【 授权许可】

CC BY   
© Song et al. 2015